In rodents, the NKR-P1 family of glycoproteins are preferentially expressed on NK cells and have been implicated in NK cell function. In this study, we describe the characterization and cloning of a human homologue. Human (h)NKR-P1A cDNA was cloned from a NK cell cDNA library by expression in COS7 cells with the use of the DX1 mAb. hNKR-P1A is a type II membrane glycoprotein with characteristic properties of the C-type lectin superfamily. Comparison of the predicted amino acid of human NKR-P1A with rat and mouse NKR-P1 indicates 46% homology. NKR-P1A is on human chromosome 12, the syntenic of mouse chromosome 6, where the murine NKR-P1 genes are located. All rat NK cells express NKR-P1; however, hNKR-P1A is present on only a subset of human NK cells. Although rodent T cells only infrequently express NKR-P1, hNKR-P1A is present on approximately 25% of adult peripheral blood T cells, including both CD4+ and CD8+ T cells, and is expressed preferentially on adult T cells with a "memory" antigenic phenotype. The anti-hNKR-P1A mAb failed to affect lysis of NK-sensitive targets; however, the spontaneous cytotoxicity mediated by certain NK cell clones against the murine P815 cell target was blocked by anti-hNKR-P1A mAb. Our findings demonstrate that NKR-P1A is a human homologue of the rodent NKR-P1 genes and suggest that this molecule may be involved in NK cell function.